1. Field of the Invention
Embodiments of the present invention relate generally to mineral based microparticles and methods for the production thereof. Embodiments of the present invention relate further to novel biodegradable and/or bioerodible microparticles having as a major component an inorganic calcium compound. Embodiments of the present invention also relate to methods of producing such microparticles by using a novel emulsion technique. The microparticles are useful in the controlled delivery of desired agents, such as biologically active agents and, given their biocompatability, are useful as injectable or implantable drug delivery vehicles. Embodiments of the present invention also relate to novel controlled drug delivery vehicles produced by coating such mineral based microparticles with a polymer, mineral or lipid shell to produce microcapsules.
2. Description of Related Art
A variety of methods to produce biodegradable drug delivery systems exist. For example, biodegradable polymer systems exist which include polylactide-co-glycolides, polycarbonates, polyalkylcyanoacrylates, and polyanhydrides. Biodegradable polymer systems have been investigated for their in vivo drug delivery capability as implants, microspheres, microcapsules, nanoparticles, aggregates, and micelles. These biodegradable polymers have been developed into useful products, and have been the subject of many review articles.
As useful as biodegradable polymers are, they have proven difficult to develop into practical parenteral systems, in part because they release drugs by a complex combination of mechanisms including homogeneous hydrolysis, enzymatic hydrolysis, diffusion, percolation, and matrix degradation. For example, the release of drugs from polylactide-co-glycolide microspheres typically involves an early burst, presumably because drug near the surface dissolves quickly, and a late burst produced after the polymer lattice has degraded sufficiently to allow more deeply confined drug to escape. Although complex polymeric media have been developed into promising biodegradable delivery systems, there remains a real need for alternative matrices which have a simpler release mechanism and which lead more readily to uniform rates of drug delivery. Such delivery systems should be biocompatible, chemically inert, cleanly resorbable, easily made, easily injectable or implantable and readily able to be coated with compounds designed to alter degradation and delivery of a biologically active agent.
Calcium sulfates have been proposed in forming matrices in non biodegradable nylon microcapsules using an emulsion interfacial polymerization technique. See, McGinity et al. J. Poly. Sci., Vol. 70, page 372 (1981); Cuff et al. J. Microencapsulation, Vol. 1, page 27 (1984). Calcium phosphates, including hydroxyapatite and carbonated hydroxyapatite have been proposed for dental and bone cements. See, Brown et al. U.S. Pat. No. 4,612,053, and U.S. Pat. Nos. 5,053,212, 5,178,845, 5,336,264, and 4,880,610 to Constantz. Similarly, calcium sulfates have been proposed as bone cements. See, Peltier et al., American Journal of Surgery, Vol. 97, pages 311-315, March 1959. These references, however, fail to provide biodegradable mineral based microparticles or an advantageous method for their production.